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Protective effects of a unique combination of nutritionally active ingredients on risk factors and gene expression associated with atherosclerosis in C57BL/6J mice fed a high fat diet

Moss, Joe W. E., Williams, Jessica O., Al-Ahmadi, Wijdan, O'Morain, Victoria, Chan, Yee-Hung, Hughes, Timothy R., Menendez-Gonzalez, Juan B., Almotiri, Alhomidi, Plummer, Sue F., Rodrigues, Neil P., Michael, D. R. and Ramji, Dipak P. 2021. Protective effects of a unique combination of nutritionally active ingredients on risk factors and gene expression associated with atherosclerosis in C57BL/6J mice fed a high fat diet. Food and Function 10.1039/D0FO02867C

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Abstract

Atherosclerosis, an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease, is responsible for one in three global deaths. Consumption of active food ingredients such as omega-3 polyunsaturated fatty acids, flavanols and phytosterols have many beneficial effects on cardiovascular disease. However, their combined actions on risk factors for atherosclerosis remains poorly understood. We have previously shown that a formulation containing each of these active components at physiologically relevant doses modulated several monocyte/macrophage processes associated with atherosclerosis in vitro, including inhibition of cytokine-induced pro-inflammatory gene expression, chemokine-driven monocyte migration, expression of M1 phenotype markers, and promotion of cholesterol efflux. The objective of the present study was to investigate whether the protective actions of the formulation extended in vivo and to delineate the potential underlying mechanisms. The formulation produced several favourable changes, including higher plasma levels of HDL and reduced levels of macrophages and myeloid-derived suppressor cells in the bone marrow. The mRNA expression of liver-X-receptor-α, peroxisome proliferator-activated receptor-γ and superoxide dismutase-1 was induced in the liver and that of interferon-γ and the chemokine (C-X-C motif) ligand 1 decreased, thereby suggesting potential mechanisms for many beneficial effects. Other changes were also observed such as increased plasma levels of triglycerides and lipid peroxidation that may reflect potential activation of brown fat. This study provides new insights into the protective actions and the potential underlying mechanisms of the formulation in vivo, particularly in relation to risk factors together with changes in systemic inflammation and hepatic lipid alterations associated with atherosclerosis and metabolic syndrome, and supports further assessments in human trials.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
Biosciences
Additional Information: Attribution 3.0 Unported (CC BY 3.0)
Publisher: Royal Society of Chemistry
ISSN: 2042-6496
Funders: British Heart Foundation
Date of First Compliant Deposit: 10 March 2021
Date of Acceptance: 26 February 2021
Last Modified: 17 Mar 2021 02:41
URI: http://orca.cf.ac.uk/id/eprint/139401

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